Human herpes virus 6 (HHV-6) is a recently discovered virus to which 95% of adults are seropositive. It was originally isolated from patients with HIV and has been associated with illness in healthy and immunocompromised children and adults, including fever, rash, hepatitis and pneumonitis. In vitro studies by several laboratories suggest that HHV-6 may exacerbate HIV replication. Our preliminary studies indicate in vivo HHV-6 is found in highest concentrations in peripheral blood early in the course of HIV infection. Our proposed studies expand upon these observations to evaluate the effects HHV-6 has on HIV replication and progression. A cross- sectional study will quantitatively examine the relationship between HIV and HHV-6 reactivation. A prospective study will assess the relationship between high levels of circulating HHV-6 and successive decreases in CD4 lymphocyte counts, a marker of HIV progression. This approach predispose to more rapid progression thereafter. The third and last Specific Aim of this proposal is directed toward evaluating the role primary HHV-6 infection plays in idiopathic episodes of pneumonitis in HIV-infected children. These studies should define whether HHV-6 influences the course of HIV-1 and whether it is an opportunistic infection in HIV infected persons.